Cross-reactive T cell responses induced by a primary dengue virus infection may contribute to increased disease severity following heterologous infections with a different virus serotype in a phenomenon known as the original antigenic sin. In this study, we developed and analyzed in-host models of T cell responses to primary and secondary dengue virus infections that considered the effect of T cell cross-reactivity in disease enhancement. We fitted the models to published patient data and showed that the overall infected cell killing is similar in dengue heterologous infections, resulting in dengue fever and dengue hemorrhagic fever. The contribution to overall killing, however, is dominated by non-specific T cell responses during the majority of secondary dengue hemorrhagic fever cases. By contrast, more than half of secondary dengue fever cases have predominant strain-specific T cell responses with high avidity. These results support the hypothesis that cross-reactive T cell responses occur mainly during severe disease cases of heterologous dengue virus infections.

中文翻译：

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在登革热病毒感染中模拟原始抗原罪。

由原发性登革热病毒感染诱导的交叉反应性T细胞应答可能会导致异种感染后出现不同的病毒血清型，从而导致疾病严重程度增加，这种现象被称为原始抗原性罪。在这项研究中，我们开发并分析了宿主细胞对原发性和继发性登革热病毒感染的T细胞反应模型，该模型考虑了T细胞交叉反应性在疾病增强中的作用。我们将模型与已发布的患者数据进行了拟合，结果表明在登革热异源感染中总体感染细胞的杀伤作用相似，从而导致了登革热和登革出血热。然而，在大多数继发性登革热出血热病例中，非特异性T细胞反应占总体杀伤力的主导。相比之下，超过一半的继发性登革热病例具有高亲和力的主要菌株特异性T细胞反应。这些结果支持以下假设：交叉反应性T细胞反应主要发生在异源登革热病毒感染的严重疾病病例中。